How to ensure good practices for documentation of safety variations

By Ea Dige

Ensuring good practices for documentation and management of safety variations, starts by optimizing the cooperation between your Regulatory Affairs (RA) and Pharmacovigilance (PV) functions.

Good practices for documentation of safety variations will support implementation of the safety finding, and being prepared for questions that may occur during a PV inspection.

According to the guidelines of Good PV Practice (GVP II.B.6), safety variations should be presented in the Pharmacovigilance System Master File (PSMF):

  • Section 6: Company specific targets for key performance indicators (KPIs).
  • Annex F: State actual timelines.

Your company’s good practices for variations should specify the following:

1. Timely submissions of safety variations initiated by:
– the company
– PRAC (the Pharmacovigilance Risk Assessment Committee).
2. Documentation of safety variation submission timelines.

Implementation and timeline
The targeted timeline for the implementation of the Summary of Product Characteristics and Package Leaflets (SmPCs/PLs) should be described in company procedures and in the PSMF.

This description should include:

  • Timing of new PLs in the packs.
  • Timing of upload of SmPCs to all public websites.
  • Review and considerations regarding the potential impact of SmPC/PIL updates on other materials (educational, promotional, clinical trial related).

Get guidance and support to get it right

At PharmAdvice we are specialized in supporting companies to accomplish:

  • Timely submission of safety variations.
  • Tracking of timelines for implementation of updates following approval.
  • Revision of processes and SOPs that describe the required cooperation between the PV and RA.

For questions and support in regards to Safety Variations, please contact Ea Dige.

Contact information

For an initial talk, please feel free to contact Ea directly at: +45 4450 3203, or via

Ea DigePharmacovigilance Manager and QPPV, MD
Ea has more than 20 years of experience from the international pharmaceutical industry with special focus on post-marketing safety surveillance, surveillance of safety during clinical trials and previous experience as Medical Assessor at the Danish Health and Medicines Authority.